In the transition from Japanese Anime to big-budget American movie, obviousely there's a lot that's going to have to be altered for American audiences to not get confused. But the big question is, are the things that will likely get changed the things that essentially make Evangelion enjoyable in the first place? I don't know, it all depends on what they're changing.
In American movies, we prefer stories that are easily acsessable, and if you're a casual viewer you'll have no problem understanding it, but on further inspection, fans can find a lot of depth and meaning. A prime example would be the Lord of the Rings series, particularly the books). You don't have to read into the deeper meaning or details to "get" that Frodo leaves the shire, and must throw the ring into mount doom while it tries to tempt, corrupt, and torment him. But if you look deeper into it, you find more meaning.
The problem with Evangelion is that the plot is like an onion - to actually "get it", you have to tear through and analyze many layers, and by the time you've reached the core, most people will already be crying from the effort. If you sat down average joe and had him watch all of the show and EoE, and asked him "OK, what was the basic story?" he'd probably reach for a bottle of tylenol. To even understand the narrative of the series, you need to seep yourself in all thing Evangelion, and even then you're still likely to be left puzzled.
It's inevitable that the movie will be "dumbed down", but that's not necessarily a bad thing depending on how much they dumb it down by, and what they're dumbing down. Really, the core of Evangelion to me is angst. It's the ultimate emo story, as in real emo, not guyshadow and wrist cutting. The emphasis of the movie will likely be on that Shinji is a very troubled kid who lost his mother and was rejected by his father, and is now expected to take on the colossal task of protecting the world during the most akward period of his emotional, mental, and physical developement (in this way, Spider-Man is very much real emo, as well), and trying to find his self worth through others rather than himself.
The exact details of the circumstances around him, I think are fair game for some slight alterations so as not to loose audiences. An example of how things might change would be say, they make the Angels be more or less depicted as some sort of force of nature that's awakened when SEELE starts playing god by trying to initiate instrumentality, which is why they give them their moniker (a sort of inside-joke they have that they're being punished by God for their plans), and so the human/angel hybrid Evangelions are created to fend them off while they work their agenda. That example would obviousely be quite a bit different from the Anime, but something like that would be an "understandable" version for western audiences, who likely wouldn't understand the japanese version for beans.
There are many ways that they might alter the details of the basic premise and plot, but these changes will be necessary for the sake of making it acsessable to western audiences. To me, details are not important. I did not cringe in Batman Begins when Bruce Wayne trained under Ra's Al Ghul, who's primary motivation was to cleanse humanity of their corrupt societies rather than cleansing the planet of humanity, because it helped give the movie a smooth-flowing narrative that was understandable, yet still had room for depth and conversation. It's the movie version of Batman, and even though it's different (and some would say "dumbed down") it's still good stuff, and likewise the Evangelion movie will be the "American movie version" versus the "Japanese anime version".
The kind of changes that would tick me off would be like if they made Shinji be 20 years old and named "Sean Isaacs" (and almost completely devoid of angst), made the Angels simply be alien invaders, and eliminated any sort of underlying instrumentality conspiracy, opting for a straightforward "Guy in giant robot must fight the aliens and win" plot. That would not even be Evangelion anymore, and hopefully that's not what they're planning.